The mechanism of cellular differentiation of Rana pipiens neural plate derivatives is being studied using tyrosine metabolizing enzymes as markers for the differentiated state. Our objective is to gain information about the relationship between embryonic induction (specific cell programming) and the specific transcriptional, translational and post-translational control of the genes for tyrosine oxidase (TDO) and DOPA-decarboxylase (DD). The time of appearance during development of enzymatically inactive TDO as measured by radioimmunoprecipitation is now known. We also have information about the time and mechanism of activation of the zymogen during later development, and we have determined that cultured chordamesodermal cells (the normal "inducer" for the neural plate) export a family of macromolecules, some of which induce the appearance of radioimmunoprecipitable TDO in cultured "indifferent" gastrula ectodermal cells. Finally, we have isolated and characterized mRNATDO during the time course of early development. The mRNATDO first appears at the conclusion of gastrulation. Thus, first transcription and translation of the gene(s) are coordinate with primary embryonic induction. Planned studies fall into three categories in terms of major objectives. The first objective is to characterize the TDO gene using DNA selected from a Rana pipiens gene library. The second is to study the causal relationship between primary embryonic induction and the first transcription of the TDO gene using cloned cDNATDO as a probe. The third objective is to begin a new study on the control of transcription and translation of the DOPA-decarboxylase gene which appears to be controlled coordinately with the TDO gene during embryonic induction. Information that we have gained concerning normal control devices in cellular differentiation is expected to be important for an understanding of phenomena (such as cancer) that involve the escape of cells from such controls.